A new quality of life consultation template for patients with venous leg ulceration.

OBJECTIVE: Chronic venous leg ulcers (CVLUs) are common and recurrent, however, care for patients predominantly has a focus which overlooks the impact of the condition on quality of life. The aim of this study was to develop a simple, evidence-based consultation template, with patients and practitioners, which focuses consultations on quality of life themes. METHOD: A nominal group was undertaken to develop a new consultation template for patients with CVLUs based on the findings of earlier qualitative study phases. RESULTS: A user-friendly two-sided A4 template was designed to focus nurse-patient consultations on the quality of life challenges posed by CVLUs. CONCLUSION: CVLUs impact negatively on the quality of life of the patient but this receives inadequate attention during current consultations. This new template will help to ensure that key concerns are effectively raised, explored and addressed during each consultation. DECLARATION OF INTEREST: The NHS West Midlands Strategic Health Authority funded this study. The authors have no conflicts of interest to declare.

The impact of chronic venous leg ulcers: a systematic review.

OBJECTIVE: Chronic venous leg ulcers are common, intractable and often recurrent, but care tends to be wound focused, potentially overlooking the significant impact the condition has on patients' lives. A systematic review was undertaken to explore the factors that impact on the quality of life of patients with chronic venous leg ulceration. METHOD: Eligible articles published between 1990 and 2013 were identified via electronic searches of research databases (MEDLINE, CINAHL, BNI, EMBASE, PsycINFO, AMED and HMIC, Cochrane Collaboration database and Google Scholar). RESULTS: There were 23 studies (11 qualitative and 12 quantitative) that met the inclusion criteria. There were then the subject of a full review. The qualitative studies were collapsed into four core themes: physical, psychological, social implications and the nurse-patient relationship. The quantitative studies were grouped according to the tool applied. The review demonstrated that chronic venous leg ulcers impact negatively upon all areas of daily living. Pain, exudate, odour and the impact on mobility were daily challenges. The ability to engage with everyday functioning was restricted either owing to the ulcer, the dressing or to a self-imposed isolation in response to the impact of symptoms. Depression and low mood were common and yet, despite this, some studies reported that participants remained hopeful. CONCLUSION: Studies suggest that chronic venous leg ulceration negatively affects the quality of life of the patient and that such issues receive inadequate attention during current consultations. If such negative implications are to be effectively addressed, key issues need to be considered during every consultation. DECLARATION OF INTEREST: This study was funded by West Midlands Strategic Health Authority. The authors have no conflicts of interest to declare.

Nurse-patient consultations in primary care: do patients disclose their concerns?

OBJECTIVE: To quantify the extent to which patients disclose their concerns to community nurses during wound care consultations. METHOD: Using an 'observation checklist' based on themes and subthemes that were identified in a previous study of the same patients, 20 wound care consultations were observed. The non-participant observer completed the checklist and made field notes regarding the context and nature of interactions. RESULTS: Patient participants had 160 opportunities to raise concerns regarding previously-identified pain, exudate and odour, yet they did not do so on 64 (40%) occasions. They had 28, 32 and 84 opportunities to raise emotional, wound care and daily living issues, respectively, and they did not on 16 (56%), 3 (9%) and 32 (38%) occasions. Overall, patients did not raise 38% of their concerns. Of the concerns that were raised, 8% were either not acknowledged or were disregarded by their community nurse. CONCLUSION: If these data are representative, this has profound implications for person-centred care and shared decision-making models of care, which are predicated on patients articulating their needs. They also have implications for the development of practitioners' communication and consulting skills.

Patient perspectives of their leg ulcer journey.

OBJECTIVE: To understand the personal impact of venous leg ulceration from the patients' perspective. METHOD: Face-to-face, unstructured interviews were conducted with nine patient participants with venous leg ulcers. The interviews were digitally recorded, transcribed verbatim and, using thematic analysis, the themes and subthemes which impacted on quality of life were identified. RESULTS: Four core themes were identified: the ulcer, symptoms, wound management and effects on daily life, with 16 subthemes that negatively impacted on quality of life (QoL) also identified. CONCLUSION: This qualitative study offers a valuable insight into the complex issues that impact on daily living for this patient group. The implications of the findings are far reaching and suggest that proactive symptom management and the fostering of a patient focus to consultations may improve QoL and encourage the patient to engage as an active partner in his/her management plan; both of which are explored in the subsequent phases of the larger study. DECLARATION OF INTEREST: This study was funded by West Midlands Strategic Health Authority. The authors have no conflicts of interest to declare.

The implementation of the Gynaecological Groupe Européen de Curiethérapie - European Society for Therapeutic Radiology and Oncology radiobiology considerations in the conversion of low dose rate to pulsed dose rate treatment schedules for gynaecological brachytherapy.

AIMS: This paper details the considerations and calculations made by this centre for the implementation of the biologically equivalent dose in 2 Gy fractions (EQD2) radiobiology calculations recommended by the Gynaecological Groupe Européen de Curiethérapie - European Society for Therapeutic Radiology and Oncology, in converting our cervix, body of uterus and vaginal vault low dose rate (LDR) treatment prescription schedules for caesium-137 to equivalent pulsed dose rate (PDR) protocols using iridium-192. MATERIALS AND METHODS: The assumptions made in order to calculate the EQD2 for both the LDR and the corresponding PDR schedules are detailed. The source geometries and prescription points are discussed for all standard treatment schedules. The prescription point for vaginal vault treatments has been altered to a 5 mm depth rather than the applicator surface, and the prescribed dose for all applicator sizes has been normalised at this depth. RESULTS: The calculated PDR schedules are presented, with corresponding target and organ at risk values given for LDR and PDR versions of standard treatment schedules. A standard 32.5 Gy point A cervix prescription used in Manchester with LDR has been converted to 2 × 19 Gy for PDR. CONCLUSIONS: PDR schedules have been calculated to correspond with our established LDR treatments in terms of EQD2 dose to the target. There is a theoretical improvement in the therapeutic ratio due to a reduction in the calculated EQD2 to organs at risk.

Astrocytes are important mediators of Aß-induced neurotoxicity and tau phosphorylation in primary culture.

Alzheimer's disease (AD) is pathologically characterised by the age-dependent deposition of ß-amyloid (Aß) in senile plaques, intraneuronal accumulation of tau as neurofibrillary tangles, synaptic dysfunction and neuronal death. Neuroinflammation, typified by the accumulation of activated microglia and reactive astrocytes, is believed to modulate the development and/or progression of AD. We have used primary rat neuronal, astrocytic and mixed cortical cultures to investigate the contribution of astrocyte-mediated inflammatory responses during Aß-induced neuronal loss. We report that the presence of small numbers of astrocytes exacerbate Aß-induced neuronal death, caspase-3 activation and the production of caspase-3-cleaved tau. Furthermore, we show that astrocytes are essential for the Aß-induced tau phosphorylation observed in primary neurons. The release of soluble inflammatory factor(s) from astrocytes accompanies these events, and inhibition of astrocyte activation with the anti-inflammatory agent, minocycline, reduces astrocytic inflammatory responses and the associated neuronal loss. Aß-induced increases in caspase-3 activation and the production of caspase-3-truncated tau species in neurons were reduced when the astrocytic response was attenuated with minocycline. Taken together, these results show that astrocytes are important mediators of the neurotoxic events downstream of elevated Aß in models of AD, and suggest that mechanisms underlying pro-inflammatory cytokine release might be an important target for therapy.

Identification of a novel region of the GABA(B2) C-terminus that regulates surface expression and neuronal targeting of the GABA(B) receptor.

GABA(B) is a G protein-coupled receptor composed of two subunits, GABA(B1) and GABA(B2). GABA(B1) contains an endoplasmic reticulum-retention sequence and is trafficked to the cell surface only in association with GABA(B2). To determine whether the C-terminus of GABA(B2) regulates GABA(B) trafficking, we constructed forms of GABA(B2) with various C-terminal truncations and examined their surface expression. Truncation of GABA(B2) after residue 841 significantly reduced surface expression of both the subunit and the heterodimerized receptor. Turnover of the Delta841 construct, however, did not differ from that of full-length GABA(B2). To determine whether the C-terminus of GABA(B2) might target GABA(B) to neurites, cultured hippocampal neurons were transfected with the truncated GABA(B2) constructs. Truncation of GABA(B2) at residue 841 resulted in primarily somatic localization; furthermore, axonal trafficking of this construct was significantly more restricted than dendritic trafficking. Finally, to biochemically assess trafficking of the truncated GABA(B2) constructs, we digested transfected HEK293 cell lysates with endoglycosidase H. When GABA(B2) was truncated at residue 841, it became sensitive to digestion by this enzyme, indicating incomplete trafficking. Taken together, these data show that the region of the GABA(B2) C-terminus between residues 841 and 862 is important for regulating forward trafficking and neuronal targeting of the GABA(B) receptor.

Comparison between margin-growing algorithms in radiotherapy software environments.

Margin-growing algorithms are commonly used tools that are available within virtual simulation and treatment planning software. We report on the accuracy of the margin-growing algorithms available in six commercially available radiotherapy software environments. A phantom containing two differently sized spheres and two rods (one level and one inclined) was constructed and scanned by CT with 1.25 mm, 2.5 mm, 3.75 mm and 5 mm slice thicknesses. The objects were outlined on a GE Advantage Simulator, and the outlined volumes recorded. Images and structures were transferred to MasterPlan, Xio, Pinnacle, Eclipse and Prosoma, where imported volumes were recorded. The contours on each system were grown isotropically by 10 mm, 20 mm and 30 mm, and volumes for each grown contour were recorded. Transfer of structure sets created in GE Advantage Simulator to the other software environments showed that the reported volumes of the four structures differ on each system. Results showed no correlation between volume accuracy and slice thickness. In general, margin growth of up to 30 mm for the rods and spheres is shown to be consistent between systems to within 1.33 mm for all slice thicknesses. Slice thickness did not appear to influence the accuracy of margin growth. Although this work highlights apparent differences in the reported volumes grown from the same original structure sets, the significance of this aspect of the planning process needs to weighed against reported intra- and inter-clinician variability in contour definition. It is not unreasonable, however, to expect that software packages should at least be consistent in volume information provided to the user.

Uridine enhances neurite outgrowth in nerve growth factor-differentiated PC12 [corrected].

During rapid cell growth the availability of phospholipid precursors like cytidine triphosphate and diacylglycerol can become limiting in the formation of key membrane constituents like phosphatidylcholine. Uridine, a normal plasma constituent, can be converted to cytidine triphosphate in PC12 [corrected] cells and intact brain, and has been shown to produce a resulting increase in phosphatidylcholine synthesis. To determine whether treatments that elevate uridine availability also thereby augment membrane production, we exposed PC12 [corrected] cells which had been differentiated by nerve growth factor to various concentrations of uridine, and measured the numbers of neurites the cells produced. After 4 but not 2 days uridine significantly and dose-dependently increased the number of neurites per cell. This increase was accompanied by increases in neurite branching and in levels of the neurite proteins neurofilament M [corrected] and neurofilament 70. Uridine treatment also increased intracellular levels of cytidine triphosphate, which suggests that uridine may affect neurite outgrowth by enhancing phosphatidylcholine synthesis. Uridine may also stimulate neuritogenesis by a second mechanism, since the increase in neurite outgrowth was mimicked by exposing the cells to uridine triphosphate, and could be blocked by various drugs known to antagonize P2Y receptors (suramin; Reactive Blue 2; pyridoxal-phosphate-6-azophenyl-2',4' disulfonic acid). Treatment of the cells with uridine or uridine triphosphate stimulated their accumulation of inositol phosphates, and this effect was also blocked by pyridoxal-phosphate-6-azophenyl-2',4' disulfonic acid. Moreover, degradation of nucleotides by apyrase blocked the stimulatory effect of uridine on neuritogenesis. Taken together these data indicate that uridine can regulate the output of neurites from differentiating PC12 [corrected] cells, and suggest that it does so in two ways, i.e. both by acting through cytidine triphosphate as a precursor for phosphatidylcholine biosynthesis and through uridine triphosphate as an agonist for P2Y receptors.